Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors
- Conditions
- Squamous Cell Carcinoma of the Head and NeckMetastatic MelanomaNon-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03645928
- Lead Sponsor
- Iovance Biotherapeutics, Inc.
- Brief Summary
A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL \[LN-144/LN-145 (lifileucel)\] in combination with immune checkpoint inhibitors or TIL \[LN-144/LN-145 (lifileucel) and LN-145-S1\] as a single agent therapy.
- Detailed Description
TIL \[LN-144/LN-145 (lifileucel) and LN-145-S1\] is an adoptive cell transfer therapy that utilizes an autologous TIL for the treatment of patients with unresectable or metastatic melanoma, advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, and locally advanced or metastatic non-small cell lung cancer. The adoptive cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphodepletion regimen, followed by infusion of autologous TIL followed by the administration of aldesleukin. Patients in Cohorts 1A, 1D, 2A, 3A, 3C, 3D, and 3E will receive TIL plus immune checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 245
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1A Lifileucel LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding immune checkpoint inhibitors (ICI). Cohort 2A Pembrolizumab LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding ICIs. Cohort 1A Pembrolizumab LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding immune checkpoint inhibitors (ICI). Cohort 3D Paclitaxel The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection before 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease. Cohort 1B LN-145-S1 LN-145-S1 therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor with or without a mitogen-activated extracellular signal-related kinase (MEK) inhibitor. Cohort 2A LN-145 LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding ICIs. Cohort 1C Lifileucel LN-144 Generation 3 (Gen 3) therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is BRAF V600 mutation positive, patients must have received BRAF inhibitor with or without a MEK inhibitor. Cohort 3A LN-145 LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding ICIs, or ≤ 4 lines if 2 or more of the lines are TKI therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS). Cohort 3A Pembrolizumab LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding ICIs, or ≤ 4 lines if 2 or more of the lines are TKI therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS). Cohort 3B LN-145 LN-145 therapy as a single agent in patients with Stage III or Stage IV NSCLC, who have previously received 1-3 lines of prior systemic therapy. Patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies are not required to have received prior systemic therapy with ICIs. Cohort 3C LN-145 LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of ICI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neo-adjuvant settings are allowed. Cohort 3C Ipilimumab LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of ICI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neo-adjuvant settings are allowed. Cohort 3C Nivolumab LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of ICI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neo-adjuvant settings are allowed. Cohort 1D Lifileucel The lifileucel regimen in combination with nivolumab-relatlimab in patients with Stage IIIC to IV unresectable or metastatic (advanced) melanoma who have had no prior therapy for advanced disease. Cohort 3D Pemetrexed The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection before 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease. Cohort 1D Nivolumab-relatlimab The lifileucel regimen in combination with nivolumab-relatlimab in patients with Stage IIIC to IV unresectable or metastatic (advanced) melanoma who have had no prior therapy for advanced disease. Cohort 3D Lifileucel The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection before 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease. Cohort 3D Pembrolizumab The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection before 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease. Cohort 3D Cisplatin The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection before 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease. Cohort 3D Carboplatin The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection before 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease. Cohort 3D Nab-Paclitaxel The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection before 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations, who have had no prior therapy for advanced disease. Cohort 3E Lifileucel The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection during 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations. Cohort 3E Pembrolizumab The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection during 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations. Cohort 3E Cisplatin The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection during 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations. Cohort 3E Carboplatin The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection during 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations. Cohort 3E Paclitaxel The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection during 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations. Cohort 3E Nab-Paclitaxel The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection during 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations. Cohort 3E Pemetrexed The lifileucel regimen in combination with pembrolizumab with or without pemetrexed, after tumor resection during 4 cycles of frontline platinum doublet chemotherapy plus pembrolizumab, in patients with Stage IV NSCLC without EGFR, ALK, or ROS1 driver mutations.
- Primary Outcome Measures
Name Time Method Objective Response Rate Up to 60 months To evaluate the efficacy of autologous TIL in combination with ICIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as determined by objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by Investigator
Safety Profile Measured by Grade ≥3 TEAEs Up to 60 months To characterize the safety profile of autologous TIL in combination with ICIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)
To evaluate the feasibility of producing lifileucel using tumor samples obtained before (Cohort 3D) or during (Cohort 3E) frontline platinum doublet chemotherapy and pembrolizumab in patients with Stage IV NSCLC Up to 60 months Feasibility is measured by the percentage of patients for whom lifileucel is successfully manufactured and meets release specification and defined as the number of patients with lifileucel product that meets specification divided by the total number of patients who had tumor resection.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival Up to 60 months To evaluate efficacy parameters such Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator
Overall Survival Up to 60 months To evaluate efficacy parameters such Overall Survival (OS)
Complete Response Rate Up to 60 months To evaluate efficacy parameters such Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator
Duration of Response Up to 60 months To evaluate efficacy parameters such Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator
Disease Control Rate Up to 60 months To evaluate efficacy parameters such Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator
Trial Locations
- Locations (45)
University of Colorado
🇺🇸Denver, Colorado, United States
The Royal Marsden NHS Foundation Trust
🇬🇧London, England, United Kingdom
University of Southern California
🇺🇸Los Angeles, California, United States
Universitätsklinikum Schleswig-Holstein - Campus Lübeck
🇩🇪Lübeck, Schleswig-Holstein, Germany
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Centre Léon Berard
🇫🇷Lyon, France
University Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
University of California, San Diego
🇺🇸La Jolla, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Columbia University
🇺🇸New York, New York, United States
MD Anderson at Cooper
🇺🇸Camden, New Jersey, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Attikon University General Hospital
🇬🇷Athens, Attiki, Greece
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Cantabria, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Universitaetsspital Bern
🇨🇭Bern, Switzerland
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga - Hospital General
🇪🇸Málaga, Spain
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Laiko General Hospital of Athens
🇬🇷Athens, Attiki, Greece
Universitätsspital Basel
🇨🇭Basel, Switzerland
Klinikum rechts der Isar der Technischen Universität München
🇩🇪München, Bavaria, Germany
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Guy's Hospital
🇬🇧London, England, United Kingdom